The present invention relates to dietary manipulation for the treatment of disease. More particularly, the present invention relates to the use saponins in an enteral formulation for treatment of infection and inflammation.
The last decade has seen an explosion in the exploration of the interaction between diet and disease. In particular, the effects of various amino acids and lipids in the diet on a variety of conditions including heart disease, hypercatabolic states, liver disease, immunosupresssion, and infection treatment have been uncovered. Often, the effects are far removed from the norm and as such are unexpected. One of the most important developments of this type has been the discovery that by changing the dietary lipid content, positive effects in health treatment beyond plasma fat modification could be achieved. While the early work in modifying lipid content and type in diet came from an understanding that saturated fats cause particular problems in heart disease, later work determined that not just the use of polyunsaturated fats but also the type of polyunsaturated fat was important.
There are three major families of polyunsaturated fatty acids: .omega.3, .omega.6 and .omega.9. The names are based on location of the closest double bonds to the methyl end of the fatty acid; that is, if the closest double bond is between the third and fourth carbon atoms from the methyl group, the molecule is classified as an .omega.3 fatty acid while if the double bond is between the 6th and 7th carbon atoms, it is classified as an .omega.6 fatty acid. Mammals can desaturate or elongate fatty acid chains but cannot interconvert fatty acids from one family to another. The most important dietary fatty acids are the C.sub.18 and C.sub.20 fatty acids, primarily linoleic (C18:2.omega.6), linolenic acid (C18:3.omega.3), .gamma.-linolenic acid (C18:3.omega.6) and dihomo-.gamma.linolenic acid (C20:3.omega.6). Manipulation of the content of these fatty acids changes the ratio of arachidonic, eicosapentanoic, and decahexanoic acids (C20:4.omega.6, C20:5.omega.3, and C22:6.omega.receptively) and can cause far reaching effects in terms of immunosuppression, response to hypercatabolic states, and infection. For example, U.S. Pat. No. 4,752,618, issued Jun. 21, 1988 on an application of Mascioli et al., the disclosure of which is incorporated herein by reference, discloses the beneficial effects of .omega.3 fatty acids in the treatment of infection. In U.S. Pat. No. 5,260,336, issued Nov. 3, 1993 on an application of Forse et al., the disclosure of which is also incorporated herein by reference, concerns a method of minimizing the effect of catabolic illness or infection using an oil such as olive oil which is rich in .omega.9 fatty acids. Other similar patents and articles, such as U.S. Pat. No. 4,810,726, issued. Mar. 7, 1989 on an application of Bistrian et al., the disclosure of which is also incorporated herein by reference, disclose other means of treating illness using fatty acid dietary manipulation.
The "culprit" in many diets appears to be the high level of .omega.6 fatty acids, primarily linoleic acid, a precursor for the formation of arachidonic acid which is a substrate for the production of pro inflammatory dienoic eicosanoids including PGE.sub.2 and TxA.sub.2 which can lead to elevated levels of thromboxane A.sub.2 and related prostanoids. Elevation of these prostanoids has been linked to problems in response to endotoxin challenge and other infection states. Accordingly, the new wave in diets has been to minimize the .omega.6 fatty acid content (which, although an essential fatty acid, is not needed in the quantities found in most commercial oils) while maximizing the .omega.3 fatty acids (e.g., fish oil) and .omega.9 fatty acids (e.g., olive oil). Similarly, although sesame oil has long been promoted as having medicinal benefits, it is only recently that the effects have been traced to sesamin (and its related lignans) in the sesame oil. In fact, U.S. patent application Ser. No. 08/201,682, filed Feb. 25, 1994, on an application of the same inventors, discloses that sesamin can promote resistance to infection and reduce inflammation. Thus, materials which modify lipid content in the diet may have important and surprising health effects.
The present invention uses saponins to treat infection and reduce inflammation. It has also been found that these saponins can work in concert with other agents such as fish oils to provide quicker (and consequently better) protection against infection.
Saponins are surface active triterpene or sterol glycosides. Although the saponins are found mainly in plants, they have also been found in certain marine animals such as echinoderms like starfish and sea cucumbers. Most saponins are non-toxic when taken orally, but many are toxic upon i.m. or i.v. injection. Saponins are most often ingested by man in legumes such as chick peas and soy beans. In fact, it has been theorized that legumes rich in saponins may reduce the threat of heart disease based, in part, on the finding that saponins can reduce plasma cholesterol levels in animals. See, e.g., Newman et al., Poultry Science 37 42-45(1957).
However, the main medicinal use for saponins appears to be their properties as immunostimulating substances or adjuvants. Reports of immunopotentiating advantages using saponins go back over fifty years (see, e.g., Thibault and Richou, C.R. Soc. Biol. 121 718-721 (1936)). While saponins are available from many sources, much of the work on immunostimulation has used saponins derived from the inner bark of the South American soaptree, Quillaja saponaria Molina. These saponins, normally designated as the Quill A saponins, remain the principal medicinal saponins in use today.
Although many other medicinal uses have been hypothesized for saponins, there has been no systematic proof that any effects other than use as an adjuvant is medicinally feasible. However, saponins have been found in some plants used in traditional or folk remedies. For example, saponins are present in ginseng which has long been used in Asia for treatment of a variety of conditions. Similarly, other homeopathic remedies also may contain saponins. The recent interest in homeopathic remedies has lead to a further exploration of the properties of materials such as saponins.
Accordingly, an object of the invention is to provide an enteral dietary supplement containing saponins.
Another object of the invention is to provide a means of treating infection and/or inflammation using saponins.
A further object of the invention is to provide a dietary supplement useful in improving the effects of .omega.3 fatty acids on treatment of infection.
An additional object of the invention is to provide a dietary supplement useful in improving the uptake of polyunsaturated fatty acids (e.g., EPA and DHA) in tissue.
A still further object of the invention is to provide a method of treating infection and/or inflammation using dietary manipulation.
These and other objects and features of the invention will be apparent from the following description and the claims.